The overall objective of this proposal is to elucidate the immunoregulatory properties of specific antigen/antibody complexes in vitro and in vivo. Of our three major goals, two relate to the ability of immune complexes to induce specific suppression of the antibody response to the antigen (used to form the complex) and the third relates to the finding that antigen/antibody complexes are immunogenic under certain conditions. The first goal is to further characterize suppressor T cells (Ts) that are activated in vitro with immune complexes. In addressing this objective, the mechanism of activation of Ts (including the induction of suppressor T cell circuits) with complexes will be studied. The second goal is to determine the mechanism of suppression induced in vivo with immune complexes that are formed in antibody excess. Here, the kinetics of the induction of suppression in vivo as well as the possible importance of suppressor T cells will be studied. The third goal is to examine the factors that determine the immunogenicity of complexes formed in antigen excess. To accomplish this objective, the role of T cells and the genetics of the in vivo response to immune complexes will be studied. Specific aims related to all three goals will include a study of the importance of the isotype, the idiotype, and the antigen in the immune complex on the regulatory effects induced by the complexes. The formation of immune complexes plays a role in the pathogenesis of a variety of human diseases including glomerulonephritis, rheumatoid arthritis, and systemic lupus erythematosus. Our studies of how immune complexes interact with the immune system may help elucidate the underlying causes of these immune complex diseases.